Elucidation of the mechanism of nickel sensitization could be an important contribution to occupational medicine and public health. Our experiments to develop a technique for consistent sensitization in guinea pigs has provided an important dimension on the immunological activity of nickel conjugates. Further studies include: 1) Localization of 63-nickel in skin by autoradiography utilizing liquid photographic emulsions and thin sections of skin previously profused with a carrier-tracer nickel solution. 2) The binding of nickel to skin will be studied by a radiotracer technique utilizing carrier-tracer Ni ion 2 and powdered human epidermis. Binding will be evaluated by liquid scintillation counting. Specific chemical modification of the skin (esterification, acetylation, deamination and sulfhydryl blockage) will be made. Their effects on the binding of nickel to skin may provide information on the nature and extent of nickel binding. 3) Inhibition of skin enzyme systems (lactic dehydrogenase, phosphopyruvate kinase, etc.) by nickel will be studied by conventional spectrophotometric assay procedures to determine whether enzymes are adversely affected by nickel. Study of the potential of nickel to cause dermatitis from implant prostheses and from consumer goods will be expanded. The undersigned agrees to accept responsibility for the scientific and technical conduct of the project and for provision of required progress reports if a grant is awarded as the result of this application.